1. Technical Field
The present disclosure relates to a method of calibrating a temperature sensor of a chemical microreactor and an analyzer for biochemical analyses.
2. Description of the Related Art
As is known, the analysis of nucleic acids involves, according to different modalities, preliminary steps of preparation of a specimen of biological material, amplification of the nucleic material contained therein, and hybridization of individual target or reference strands, corresponding to the sequences sought. Hybridization takes place (and the test yields a positive outcome) if the specimen contains strands complementary to the target strands.
At the end of the preparatory steps, the specimen is examined for controlling whether hybridization has taken place (the so-called “detection step”).
The preparatory steps that precede amplification can be conducted separately, using purposely provided instrumentation and reagents.
With increasing frequency, at least for the amplification of nucleic material and for the detection step, integrated chemical microreactors are used, which enable various operations to be carried out without having to transfer the material being processed. The microreactors can be provided in monolithic bodies, such as, for example, semiconductor chips, or joining chips of various materials. According to common solutions, for example, some microreactors comprise a first chip, generally made of plastic material, which houses reservoirs or wells possibly connected through microfluidic connections, and a semiconductor chip, on which heaters and temperature sensors are provided.
The microreactors are loaded with biological specimens to be analyzed and are introduced in thermocyclers to carry out biochemical analyses.
A thermocycler is configured to receive microreactors mounted on purposely provided boards and comprises in general at least a control unit, a cooling device, and a detection device.
The control unit can be connected to the microreactor through connectors and, by exploiting the temperature sensors on board the microreactor itself, controls the heaters and the cooling device for carrying out pre-determined thermal cycles.
Once the biochemical processes are completed, the detection device, which is often of an optical type, verifies whether in the specimen processed given substances (for example, given sequences of nucleotides) are present or not. The optical detection exploits in general fluorophores, which, during processing of the specimen, bind selectively to the substances to be detected.
In the execution of thermal cycles that enable performance of the biochemical processes in the microreactor, it is of fundamental importance that the temperature be controlled in an extremely precise way. For this reason, the temperature sensors on board the microreactors are calibrated individually prior to use. Currently, the calibration can be carried out only in the factory, which entails some limitations.
In the first place, the time between calibration and use can be rather long and there is consequently the risk of the characteristics of the sensors being modified.
Likewise, the environmental conditions of use of the microreactors as a rule change with respect to the calibration conditions, and also this can adversely affect the performance levels of the temperature sensors.
In addition, the calibration performed in the factory is in general costly because it uses purposely designed testing instruments and in any case involves rather long times.